PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-5 (5)
 

Clipboard (0)
None
Journals
Year of Publication
Document Types
2.  Inflammation assessment in patients with arthritis using a novel in vivo fluorescence optical imaging technology 
Annals of the Rheumatic Diseases  2011;71(4):504-510.
Background
Indocyanine green (ICG)-enhanced fluorescence optical imaging (FOI) is an established technology for imaging of inflammation in animal models. In experimental models of arthritis, FOI findings corresponded to histologically proven synovitis. This is the first comparative study of FOI with other imaging modalities in humans with arthritis.
Methods
252 FOI examinations (Xiralite system, mivenion GmbH, Berlin, Germany; ICG bolus of 0.1 mg/kg/body weight, sequence of 360 images, one image per second) were compared with clinical examination (CE), ultrasonography (US) and MRI of patients with arthritis of the hands.
Results
In an FOI sequence, three phases could be distinguished (P1–P3). With MRI as reference, FOI had a sensitivity of 76% and a specificity of 54%, while the specificity of phase 1 was 94%. FOI had agreement rates up to 88% versus CE, 64% versus greyscale US, 88% versus power Doppler US and 83% versus MRI, depending on the compared phase and parameter. FOI showed a higher rate of positive results compared to CE, US and MRI. In individual patients, FOI correlated significantly (p<0.05) with disease activity (Disease Activity Score 28, r=0.41), US (r=0.40) and RAMRIS (Rheumatoid Arthritis MRI Score) (r=0.56). FOI was normal in 97.8% of joints of controls.
Conclusion
ICG-enhanced FOI is a new technology offering sensitive imaging detection of inflammatory changes in subjects with arthritis. FOI was more sensitive than CE and had good agreement with CE, US in power Doppler mode and MRI, while showing more positive results than these. An adequate interpretation of an FOI sequence requires a separate evaluation of all phases. For the detection of synovitis and tenosynovitis, FOI appears to be as informative as 1.5 T MRI and US.
doi:10.1136/annrheumdis-2010-148288
PMCID: PMC3298665  PMID: 22388997
3.  Certolizumab pegol plus methotrexate provides broad relief from the burden of rheumatoid arthritis: analysis of patient-reported outcomes from the RAPID 2 trial 
Annals of the Rheumatic Diseases  2011;70(6):996-1002.
Objective
To assess the impact of certolizumab pegol (CZP) on patient-reported outcomes (PROs) in rheumatoid arthritis (RA), and to interpret these results using number needed to treat (NNT), and associations between PRO responses and longer term outcomes.
Methods
A total of 619 patients with active RA were randomised to CZP 200 or 400 mg, or placebo plus methotrexate (MTX). PROs assessed included pain, patient's global assessment of disease activity (PtGA), physical function, fatigue and health-related quality of life. Treatment impact on PROs, NNT to achieve simultaneous improvements in multiple PROs and correlations between PROs were calculated. Times to onset of improvements greater than or equal to minimum clinically important differences (MCIDs) in pain as a determinant of clinical outcomes at week 24 were compared between week 6 and 12 responders, and in patients with improvements in pain ≥MCID at week 12 (week 12 responders/non-responders).
Results
CZP 200 and 400 mg plus MTX were associated with rapid, clinically meaningful improvements in all PROs. The NNT for subjects to report changes ≥MCID in up to five PROs was two to three, and five for all six PROs (pain, PtGA, physical function, fatigue and short-form 36-item Physical and Mental Component Summary Scores). More patients with improvements ≥MCID in pain at week 6 than those at week 12 had lower disease activity at week 24. Week 12 pain responders had better clinical outcomes at week 24 than non-responders.
Conclusions
The data demonstrate that CZP provides broad relief from the burden of RA.
Trial registration number
NCT00160602.
doi:10.1136/ard.2010.143586
PMCID: PMC3086050  PMID: 21415050
4.  Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-α, in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study 
Annals of the Rheumatic Diseases  2011;70(9):1542-1549.
Objective
To evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles of mavrilimumab, a human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, in subjects with rheumatoid arthritis (RA).
Methods
A randomised, double-blind, placebo-controlled, dose-escalating phase I study in subjects with RA who received stable methotrexate treatment for ≥3 months before enrolment. Subjects received single intravenous escalating doses of mavrilimumab (0.01–10.0 mg/kg) or placebo.
Results
32 subjects were enrolled in this study (1 unblinded subject at 0.01 mg/kg and another at 0.03 mg/kg were followed by five sequential double-blinded cohorts, n=6 each, treated with 0.1, 0.3, 1.0, 3.0 and 10.0 mg/kg, respectively). Adverse events were mild or moderate and were reported with similar frequency across all treatment cohorts. One subject (10.0 mg/kg) experienced moderate face and neck urticaria during infusion that resolved with symptomatic treatment. Systemic clearance of mavrilimumab approached that of endogenous IgG at doses >1.0 mg/kg; pharmacodynamic activity was confirmed in the 1.0 and 3.0 mg/kg cohorts by suppression of suppressor of cytokine signalling 3 mRNA transcripts. In exploratory analyses, reductions of acute phase reactants were observed in subjects with elevated C-reactive protein (>5 mg/l) and erythrocyte sedimentation rate (≥20.0 mm/h) at baseline. No significant change in Disease Activity Score 28-joint assessment (DAS28) was seen in any of the cohorts. In mavrilimumab-treated subjects (n=15) with baseline DAS28 >3.2, mean disease activity (DAS28) was significantly reduced at 4 weeks.
Conclusion
In this first-in-human study, mavrilimumab showed preliminary evidence of pharmacodynamic activity. Importantly, the safety and pharmacokinetic profiles of mavrilimumab support further clinical studies in RA.
Trial registration number: NCT00771420.
doi:10.1136/ard.2010.146225
PMCID: PMC3147227  PMID: 21613310
5.  Performance of the new 2011 ACR/EULAR remission criteria with tocilizumab using the phase IIIb study TAMARA as an example and their comparison with traditional remission criteria 
Annals of the Rheumatic Diseases  2011;70(11):1986-1990.
Background
Remission is the established goal in rheumatoid arthritis (RA) treatment. Although originally defined by a disease activity score in 28 joints (DAS28) <2.6, more stringent criteria may imply the absence of disease activity. The 2011 ACR/EULAR remission criteria provide the newest and most stringent definition of remission.
Objectives
To evaluate post hoc the remission by ACR/EULAR criteria and compare the criteria with the conventional DAS28 in TAMARA, an open-label phase IIIb tocilizumab (TCZ) trial including patients with active RA receiving inadequate disease-modifying antirheumatic drugs (DMARDs) or tumour necrosis factor α (TNFα) inhibitor treatment.
Results
286 patients were enrolled, 99.7% of patients were receiving a conventional DMARD and 41.6% had TNFα inhibitor pretreatment. Baseline mean DAS28 of 6.0 ± 1.0 fell to 2.6 ± 1.5 at week 24. DAS28 <2.6 was achieved by 47.6% at week 24. Remission rates with the new ACR/EULAR Boolean-based criteria for clinical studies were 15.0% after 12 weeks and 20.3% after 24 weeks. Of note, 13.5% of patients with previous TNFα blocker inadequate response still achieved remission according to the new ACR/EULAR criteria after 24 weeks. Clinical Disease Activity Index and Simplified Disease Activity Index remission rates were 24.1% and 25.2%, respectively.
Conclusions
Under the definition of the new stringent 2011 ACR/EULAR remission criteria, patients with active RA despite DMARD treatment and even after inadequate response to TNFα inhibitors, receiving TCZ showed significant rates of remission. Similar remission rates were achieved, when clinical practice criteria, not inclusive of acute phase reactants, were used.
doi:10.1136/ard.2011.152678
PMCID: PMC3184242  PMID: 21875873

Results 1-5 (5)